Device and Method Employing Shape Memory Alloy

ABSTRACT

A system for the metering and delivery of small discrete volumes of liquid is comprised of a small or minimal number of inexpensive components. One such component is a movable member, such as a miniature precision reciprocating displacement pump head, which is driven by an actuator that comprises a shape memory alloy material. The operating mechanism of the system is of little or minimal complexity. The system facilitates the precise metering and delivery of the small discrete volumes of liquid. Potential applications for the system include subcutaneous, long-term, automated drug delivery, for example, the delivery of insulin to a person with diabetes. In such an application, the small, simple and inexpensive nature of the invention would allow for its use as both a portable and a disposable system.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a divisional application of co-pending parent application havingU.S. application Ser. No. 12/163,944, filed Jun. 27, 2008, which is acontinuation of U.S. application Ser. No. 11/106,256, filed Apr. 13,2005, now U.S. Pat. No. 7,399,401, which is a continuation-in-part (CIP)of U.S. application Ser. No. 10/683,659, filed Oct. 9, 2003, now U.S.Pat. No. 6,916,159, which claims benefit and priority based on U.S.Provisional Application No. 60/417,464, entitled “Disposable Pump ForDrug Delivery System,” filed on Oct. 9, 2002, U.S. ProvisionalApplication No. 60/424,613, entitled “Disposable Pump And ActuationCircuit For Drug Delivery System,” filed on Nov. 6, 2002, and U.S.Provisional Application No. 60/424,414, entitled “Automatic BiologicalAnalyte Testing Meter With Integrated Lancing Device And Methods OfUse,” filed Nov. 6, 2002, each of which is incorporated herein in itsentirety by this reference. This non-provisional application is alsorelated to U.S. Pat. No. 6,560,471, entitled “Analyte Monitoring Deviceand Methods of Use,” issued May 6, 2003, which is incorporated herein inits entirety by reference.

FIELD OF INVENTION

This invention generally relates to fluid delivery devices, systems, andmethods. This invention further relates to small volume, disposablemedical devices for the precision delivery of medicines or drugs such asinsulin, and associated systems and methods.

BACKGROUND OF THE INVENTION

Insulin pumps are widely available and are used by diabetic people toautomatically deliver insulin over extended periods of time. Allcurrently available insulin pumps employ a common pumping technology,the syringe pump. In a syringe pump, the plunger of the syringe isadvanced by a lead screw that is turned by a precision stepper motor. Asthe plunger advances, fluid is forced out of the syringe, through acatheter to the patient. The choice of the syringe pump as a pumpingtechnology for insulin pumps is motivated by its ability to preciselydeliver the relatively small volume of insulin required by a typicaldiabetic (about 0.1 to about 1.0 cm³ per day) in a nearly continuousmanner. The delivery rate of a syringe pump can also be readily adjustedthrough a large range to accommodate changing insulin requirements of anindividual (e.g., basal rates and bolus doses) by adjusting the steppingrate of the motor. While the syringe pump is unparalleled in its abilityto precisely deliver a liquid over a wide range of flow rates and in anearly continuous manner, such performance comes at a cost. Currentlyavailable insulin pumps are complicated and expensive pieces ofequipment costing thousands of dollars. This high cost is due primarilyto the complexity of the stepper motor and lead screw mechanism. Thesecomponents also contribute significantly to the overall size and weightof the insulin pump. Additionally, because of their cost, currentlyavailable insulin pumps have an intended period of use of up to twoyears, which necessitates routine maintenance of the device such asrecharging the power supply and refilling with insulin.

U.S. Pat. No. 6,375,638 of Clyde Nason and William H. Stutz, Jr.,entitled “Incremental Motion Pump Mechanisms Powered by Shape MemoryAlloy Wire or the Like,” issued Apr. 23, 2002, and naming MedtronicMiniMed, Inc. as the assignee, which patent is incorporated herein inits entirety by this reference, describes various ratchet typemechanisms for incrementally advancing the plunger of a syringe pump.The ratchet mechanisms are actuated by a shape memory alloy wire. Theembodiments taught by Nason et al. involve a large number of movingparts, and are mechanically complex, which increases size, weight andcost, and can reduce reliability.

SUMMARY OF THE INVENTION

A fluid delivery system constructed according to the present inventioncan be utilized in a variety of applications. As described in detailbelow, it can be used to deliver medication to a person or animal. Theinvention can be applied in other medical fields, such as forimplantable micro-pump applications, or in non-medical fields such asfor small, low-power, precision lubricating pumps for precisionself-lubricating machinery.

In its preferred embodiment, the present invention provides a mechanicalinsulin delivery device for diabetics that obviates the above-mentionedlimitations of the syringe pump namely size, weight, cost andcomplexity. By overcoming these limitations, a precise and reliableinsulin delivery system can be produced with sufficiently low cost to bemarketed as a disposable product and of sufficiently small size andweight to be easily portable by the user. For example, it is envisionedthat such a device can be worn discretely on the skin as an adhesivepatch and contain a three-day supply of insulin after the use of whichthe device is disposed of and replaced.

The present invention relates to a miniature precision reciprocatingdisplacement pump head driven by a shape memory alloy actuator. Shapememory alloys belong to a class of materials that undergo a temperatureinduced phase transition with an associated significant dimensionalchange. During this dimensional change, shape memory alloys can exert asignificant force and can thus serve as effective actuators. The shapememory alloy actuator provides an energy efficiency about one thousandtimes greater than that of a conventional electromechanical actuator,such as a solenoid, and a force to mass ratio about ten thousand timesgreater. Additionally, the cost of shape memory alloy materials comparesfavorably to the cost of electromechanical devices with similarcapabilities.

The device of the present invention is intended to be operated in aperiodic dosing manner, i.e., liquid is delivered in periodic discretedoses of a small fixed volume rather than in a continuous flow manner.The overall liquid delivery rate for the device is controlled andadjusted by controlling and adjusting the dosing period. Thus the deviceemploys a precision timing mechanism in conjunction with a relativelysimple mechanical system, as opposed to a complex mechanical system,such as that embodied by the syringe pump.

A precision timing device is an inherently small, simple and inexpensivedevice. It is an underlying assumption of the invention (and areasonable conclusion of process control theory) that in the treatmentof diabetes, there is no clinical difference between administeringinsulin in periodic discrete small doses and administering insulin in acontinuous flow, as long as the administration period of the discretedose is small compared to the interval of time between which the bloodglucose level is measured. For the present invention, a small dose sizeis regarded as on the order of 0.10 units of insulin (1 microliter)assuming a standard pharmaceutical insulin preparation of 100 units ofinsulin per ml (U100). A typical insulin dependent diabetic person usesbetween 10 and 100 units of insulin per day, with the average diabeticperson using 40 units of insulin. Thus the present invention woulddeliver the daily insulin requirements of the average diabetic person in400 individual discrete doses of 1 μl each with a dosing period that canbe programmed by the user. A pump constructed according to the presentinvention can have a predetermined discrete dosage volume that is largeror smaller than 1 μl, but preferably falls within the range of 0.5 to 5μl, and more preferably falls within the range of 1 to 3 μl. The smallerthe discrete dose is of a particular pump design, the more energyrequired by the device to deliver a given amount of fluid, since eachpump cycle consumes roughly the same amount of energy regardless ofdiscrete dosage size. On the other hand, the larger the discrete dosageis, the less precise the pump can mimic the human body in providing asmooth delivery rate. A device constructed according to the presentinvention is also suitable for delivery of other drugs that might beadministered in a manner similar to insulin.

It is further intended that the present invention could be used as adisposable component of a larger diabetes management system comprised ofadditional disposable and non-disposable components. For example, thepresent invention could be coupled with a continuous blood glucosemonitoring device and remote unit, such as a system described in U.S.Pat. No. 6,560,471, entitled “Analyte Monitoring Device and Methods ofUse,” issued May 6, 2003. In such an arrangement, the hand-held remoteunit that controls the continuous blood glucose monitoring device couldwirelessly communicate with and control both the blood glucosemonitoring unit and the fluid delivery device of the present invention.The monitor and pump could be physically separate units, or could shareone or more disposable and/or non-disposable components. For example, adisposable pump constructed according to the present invention andcharged with a 3-day supply of insulin, a small battery and a disposableglucose sensor could be integrated into a single housing and releasablycoupled with non-disposable components such as control electronics, atransmitter/receiver and a user interface to comprise a small insulindelivery device that could be worn on the skin as an adhesive patch.Alternatively, the battery (or batteries) and/or sensor could bereplaced separately from the disposable pump. Such arrangements wouldhave the advantage of lowering the fixed and recurring costs associatedwith use of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

A detailed description of various embodiments of the invention isprovided herein with reference to the accompanying drawings, which arebriefly described below.

FIG. 1A shows a schematic representation of a most general embodiment ofthe invention.

FIG. 1B shows a schematic representation of an alternative generalembodiment of the invention.

FIG. 2A shows a schematic representation of a preferred embodiment ofthe invention.

FIGS. 2B and 2C show enlarged details of a preferred embodiment of theinvention.

FIG. 3 shows a schematic representation of a preferred embodiment of acheck valve to be used in the invention.

FIG. 4 shows a schematic representation of a preferred embodiment of apulse generation circuit to be used with the invention.

FIG. 5 shows data from the experimental characterization of thereproducibility of a functional model of the invention.

FIG. 6 shows data from the experimental characterization of the energyutilization of a functional model of the invention.

FIG. 7 shows a schematic representation of a first alternativeembodiment of the invention.

FIG. 8 shows a schematic representation of a second alternativeembodiment of the invention.

FIG. 9 shows a schematic representation of a first alternativeembodiment of a pulse generation circuit to be used with the invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

A device of the present invention includes a miniature precisionreciprocating displacement pump driven by a shape memory alloy wirelinear actuator and controlled by a programmable pulse generatingcircuit. For purposes of description, the device is divided into threesubcomponents, a precision miniature reciprocating displacement pumphead, a shape memory alloy linear actuator, and a programmable pulsegenerating circuit. Each subcomponent is comprised of multiple elements.A schematic representation of a most general embodiment of the inventionis shown in FIG. 1A and is described below.

The miniature precision pump head is comprised of the followingelements: a rigid substrate 101 to which other components may beattached so as to fix their orientation and position relative to oneanother, a fluid reservoir 102 for storing the fluid to be pumped 103and a small cavity, henceforth referred to as the displacement cavity104, whose volume can be varied between precisely defined limits. Thelimit corresponding to a state of maximum volume for the displacementcavity 104 is defined as the first limit 105 and the limit correspondingto a state of minimum volume for the displacement cavity 104 is definedas the second limit 106. An inlet conduit 107 connects the displacementcavity 104 to the fluid reservoir 102 and thus permits fluid flowbetween the two. An inlet check valve 108 is situated within the inletconduit 107 such that fluid flow is restricted to flowing from the fluidreservoir 102 to the displacement cavity 104. An outlet conduit 109connects the displacement cavity 104 to some point 111 to which it isdesired to deliver the fluid. An outlet check valve 110 is situatedwithin the outlet conduit 109 such that fluid flow is restricted toflowing from the displacement cavity 104 to the point 111 to which it isdesired to deliver the fluid.

The shape memory alloy actuator is comprised of a shape memory allowmaterial, such as a nickel-titanium alloy material, sometimes referredto as “nitinol.” The shape memory alloy material is sensitive totemperature or heat. For example, the material temporarily shrinks at acertain temperature, or shrinkage temperature, such as about 70° C.above ambient temperature for nitinol, and expands at a relatively lowertemperature to return to its original condition. In response to beingheated to the above-described shrinkage temperature, the shape memoryalloy undergoes a dimensional change, such as a change in its length. Inthis way, a wire composed of a material such as nitinol, can undergo achange in length and a return toward its original length one or moretimes via temperature treatment or repeated temperature cycling. It iscontemplated that a material that expands by going through a phasetransition at a certain temperature and shrinks at a differenttemperature to return toward its original condition could be used.

In the process of undergoing a dimensional change, as described above,the shape alloy material goes through a reversible phase transition ortransformation, or a reversible structural phase transition, upon achange in temperature. Generally, such a transition represents a changein the material from one solid phase of the material to another, forexample, by virtue of a change in the crystal structure of the materialor by virtue of a reordering of the material at a molecular level. Inthe case of nitinol, for example, the superelastic alloy has a lowtemperature phase, or martensitic phase, and a high temperature phase,or austenitic phase. These phases can also be referred to in terms of astiff phase and a soft and malleable phase, or responsive phase. Theparticular phase transition associated with a particular alloy materialmay vary.

The shape memory alloy actuator is also comprised of the followingelements. A movable member is referred to as a plunger 112 and is fixedby a rigid restraint 113 such that it is constrained to a periodicmotion of precisely fixed limits. The plunger 112 is situated inrelation to and/or attached to the displacement cavity 104 such thatmovement of the plunger 112 within the limits of its constrained motionwill cause the volume of the displacement cavity 104 to be variedbetween its limits 105, 106. A biasing spring 115 is situated relativeto the rigid restraint 113 and the plunger 112 such that at equilibrium,the biasing spring 115 exerts a force on the plunger 112 whose directionis that which would induce the displacement cavity 104 toward a state ofminimum volume, i.e., toward its second limit 106. A length of shapememory alloy wire 114 is connected at one end to the plunger 112 and atanother end to the rigid substrate 101. The shape memory alloy wire 114is situated such that its dimensional change will give rise to motion ofthe plunger 112. The shape memory alloy wire 114 and the biasing spring115 are both of sufficient dimension such that when the shape memoryalloy wire 114 is heated so as to induce phase transition and associateddimensional change, the wire will move the plunger 112 against the forceof the biasing spring 115 “in one generally uninterrupted motion” to itssecond limit 105 so as to create a state of maximum volume within thedisplacement cavity 104, whereas when the shape memory alloy is allowedto cool to ambient temperature, the force imparted by the biasing spring115 will stretch the shape memory alloy wire 114 until the point wherethe displacement cavity 104 is in a state of minimum volume.

The programmable pulse generating circuit is comprised of a source ofelectric power 116, an electrical connection 117 from the source ofelectric power 116 to each end of the shape memory alloy wire 114 and aprogrammable pulse generating circuit 118 situated along the electricalconnection 117 such that pulses of electricity from the electric powersource 116 may be applied to the shape memory alloy wire 114automatically in a preset regular periodic manner.

Operation of the device proceeds in a cyclic manner. For purposes ofdescription the beginning of the cycle is defined as the followingstate. All void space within the fluid reservoir 102, inlet 107 andoutlet 109 conduit, inlet 108 and outlet 110 check valves anddisplacement cavity 104 are completely filled with the fluid 103 to bepumped. The shape memory alloy wire 114 is at ambient temperature andthus in a state of maximum length. Correspondingly, the position of theplunger 112 is such that the volume of the displacement chamber 104 isat its minimum value. The biasing spring 115 is in a compressed statesuch that it exerts a force on the plunger 112 consistent with a stateof minimum volume of the displacement cavity 104. Operation of thedevice involves first a heating of the shape memory alloy wire 114 to atemperature and for a period of time sufficient to induce phasetransition and an associated dimensional change. Heating of the shapememory alloy wire 114 is accomplished by passing an electric currentthough it. The duration of the electric heating period is preset and iscontrolled by the timing and switching circuit 118. The dimensionalchange of the shape memory alloy wire 114 will result in the movement ofthe plunger 112 against the opposing force of biasing spring 115 so asto vary the volume of the displacement chamber 104 toward its firstlimit 105 and a state of maximum volume. As the volume of thedisplacement cavity 104 is increased, fluid 103 is drawn into thedisplacement cavity 104 from the fluid reservoir 102 through the inletconduit 107 and inlet check valve 108. Fluid 103 is not drawn into thedisplacement cavity 104 through the outlet conduit 109 due to theone-way flow restriction of the outlet check valve 110. After the presetduration, the current is then switched off by the timing and switchingcircuit 118 allowing the shape memory alloy wire 114 to cool below itsphase transition temperature. Cooling proceeds via natural convection tothe ambient environment. When the shape memory alloy wire 114 coolsbelow its phase transition temperature, the force exerted by the biasingspring 115 stretches the shape memory alloy wire 114 to its originalmaximum length. This allows the movement of the plunger 112 so as tovary the volume of the displacement cavity 104 toward its second limit106 and a state of minimum volume. As the volume of the displacementcavity 104 is decreased, fluid 103 is pushed out of the displacementcavity 104 through the outlet conduit 109 and outlet check valve 110.Fluid 103 is not pushed out of the displacement cavity 104 through theinlet conduit 107 due to the one-way flow restriction of the inlet checkvalve 108. Thus one complete heating and cooling cycle of the shapememory alloy wire 114 results in the delivery of a volume of fluid 103from the fluid reservoir 102 to the end of the outlet conduit 111. Thevolume of fluid delivered with each cycle is precisely equal to thedifference between the maximum and minimum volumes of the displacementcavity 104 as determined by the precisely defined limits 105, 106. Theoverall rate of fluid delivery is controlled by varying the period oftime between actuations of the shape memory alloy actuator 104.

AN ALTERNATIVE GENERAL EMBODIMENT OF THE INVENTION

A schematic representation of an alternative general embodiment of theinvention is shown in FIG. 1B. The alternative general embodimentincludes all of the same components and elements as the generalembodiment shown in FIG. 1A with the following exceptions. In thisembodiment of the invention, heating of the shape memory alloy material114 so as to cause a phase transition associated shortening of itslength results in a minimum volume condition for the displacement cavity104. This may be achieved, for example, through the use of a pivotinglinkage assembly 119 connecting the biasing spring 115 to the plunger112.

DETAILED DESCRIPTION OF A PREFERRED EMBODIMENT OF THE INVENTION

As stated previously, it is an intention of the present invention thatit be sufficiently small and sufficiently inexpensive to be practicallyused as both a portable device and as a disposable device. For example,a device that can be comfortably worn on the skin as an adhesive patchand can be disposed of and replaced after 3 days of use. A preferredembodiment of the invention includes specific embodiments of the variouselements and components of the general embodiment that are consistentwith this intention.

A preferred embodiment of the invention is diagrammed schematically inFIGS. 2A, 2B and 2C and is comprised of all of the same elements andcomponents of the general embodiment of the invention shown in FIGS. 1Aand 1B with the following exceptions. In a preferred embodiment of theinvention the displacement cavity is comprised of an elastomericdiaphragm pump head 201. An enlarged view of the details of thediaphragm pump head 201 is shown by FIG. 2B with pump head 201 in astate of minimum volume and by FIG. 2C with pump head 201 in a state ofmaximum volume. The diaphragm pump head is comprised of an elastomericdiaphragm 202 set adjacent to a rigid substrate 203 and scaled about aperimeter of the elastomeric diaphragm 202. The displacement cavity 204is then comprised of the volume in between the adjacent surfaces of therigid substrate 203 and the elastomeric diaphragm 202 within the sealedperimeter.

Separate inlet 205 and outlet 206 conduits within the rigid substrate203 access the displacement volume of the elastomeric diaphragm pumphead 201 with the inlet conduit 205 connecting the displacement cavity204 with a fluid reservoir 207 and the outlet conduit 206 connecting thedisplacement cavity 204 to the point to which it is desired to deliverfluid 208. An inlet check valve 209 and an outlet check valve 210 aresituated within the inlet conduit 205 and outlet conduit 206respectively, oriented such that the net direction of flow is from thefluid reservoir 207 to the point to which it is desired to deliver fluid208.

The plunger 211 is comprised of a cylindrical length of rigid dielectricmaterial. The plunger 211 is situated within a cylindrical bore 212 of arigid restraint 213 such that the axis of the plunger 211 is orientednormal to surface of the elastomeric diaphragm 202. The flat head of theplunger 211 is functionally attached to the non-wetted surface ofelastomeric diaphragm 202 opposite the displacement cavity 204 such thatmovement of the plunger 211 along a line of motion coincident with itsaxis will cause the concomitant variation in the volume of thedisplacement cavity 204. The biasing spring 214 is situated within thecylindrical bore 212 of the rigid restraint 213, coaxial with theplunger 211. The relative positions and dimensions of the plunger 211,the rigid restraint 213 and the biasing spring 214 are such that atequilibrium the biasing spring 214 exerts a force on the plunger 211along a line coincident with its axis such that the displacement cavity204 is in a state of minimum volume (FIG. 2A).

A straight length of shape memory alloy wire 215 is situated in aposition coincident with the axis of the plunger 211. One end of theshape memory alloy wire 215 is fixed to the rigid restraint 203 andelectrically connected by connection 216 to the programmable pulsegenerating circuit 217 and the electric power source 218. The other endof the shape memory alloy wire 215 along with an electrical connection219 to that end is connected to the end of the plunger 211. The shapememory alloy wire 215 and the biasing spring 214 are both of sufficientdimension such that when the shape memory alloy wire 215 is heated so asto induce phase transition and associated dimensional change, it willpull the plunger 211 against the force of the biasing spring 214 so asto create a state of maximum volume within the displacement cavity 204,whereas when the shape memory alloy is allowed to cool to ambienttemperature, the force imparted by biasing spring 214 will stretch theshape memory alloy wire 215 until the point where the displacementcavity 204 is in a state of minimum volume.

A preferred embodiment of an inlet and outlet check valve is shown incross-section in FIG. 3 and is comprised of a molded one-pieceelastomeric valve which can be press-fit into the inlet or outletconduit. An important feature for a check valve appropriate for use inthe present invention is that it possesses a low cracking pressure andprovides a tight seal in the absence of any back pressure. A preferredembodiment of such a check valve is comprised of a thin-walledelastomeric dome 301 situated on top of a thick elastomeric flange 302.The top of the dome has a small slit 303 cut through it that is normallyclosed. A fluid pressure gradient directed toward the concave side 304of the dome will induce an expansion of the dome 301 forcing the slit303 open so as to allow fluid to flow through the valve in thisdirection. A fluid pressure gradient directed toward the convex side 305of the dome will induce a contraction of the dome 301 forcing the slit303 shut so as to prohibit fluid to flow through the valve in thisdirection.

A preferred embodiment of a pulse generating circuit is shown in FIG. 4and is comprised of a 200 milliamp-hour, lithium-manganese oxide primarybattery 401, a high capacitance, low-equivalent series resistance (ESR)electrochemical capacitor 402, a programmable digital timing circuit403, and a low-resistance field effect transistor switch 404. The shapememory alloy wire is indicated in FIG. 4 symbolically as a resistor 405.The battery 401 and electrochemical capacitor 402 are electricallyconnected to each other in parallel and are connected to the shapememory alloy wire 405 through the transistor switch 404. Theprogrammable timing circuit 403, also powered by the battery 401, sendsa gating signal to the transistor switch 404, as programmed by the userin accordance with the user's pumping requirements. During the period oftime for which the transistor switch 404 is open, the battery 401 willkeep the electrochemical capacitor 402 at a state of full charge. Duringthe period of time for which the transistor switch 404 is closed, powerwill be delivered to the shape memory alloy wire 405, primarily from theelectrochemical capacitor 402 rather than from the battery 401, owing tothe substantially lower ESR associated with the electrochemicalcapacitor 402. As such, the battery 401 is substantially isolated fromthe high current draw associated with the low resistance of the shapememory alloy wire 405 and the useful life of the battery 401 issignificantly extended.

A preferred embodiment of a fluid reservoir 207 appropriate for use withthe present invention is one for which the volume of the fluid reservoirdiminishes concomitantly as fluid is withdrawn such that it is notnecessary to replace the volume of the withdrawn fluid with air or anyother substance. A preferred embodiment of a fluid reservoir 207 mightcomprise a cylindrical bore fitted with a movable piston, for example, asyringe, or a balloon constructed of a resilient material.

Operation of the preferred embodiment of the invention proceeds in amanner analogous to that described for the most general embodiment. Inaddition to its simplicity, the preferred embodiment has the advantageof physically blocking any fluid flow from the fluid reservoir to thepoint to which it is desired to deliver the fluid when there is no powerbeing supplied to the system. This provides additional protectionagainst an overdose caused by fluid expanding or being siphoned throughthe check valves when the system is inactive.

DETAILED DESCRIPTION OF A FUNCTIONAL MODEL OF THE INVENTION

A functional model of a preferred embodiment of the invention has beenconstructed and its performance has been characterized. The functionalmodel is similar in appearance to the preferred embodiment of theinvention shown in FIGS. 2, 3 and 4 and is described in more detailbelow. The fixed rigid components of the pump including the rigidrestraint and the rigid substrate of the diaphragm pump head are eachmachined from a monolithic block of acetal. Inlet and outlet conduitsare additionally machined out of the same block. Check valves arecommercially available one-piece elastomeric valves (for example, CheckValve, Part # VA4914, available from Vernay Laboratories Inc. of YellowSprings, Ohio). A length of shape memory alloy actuator is 40 mm longand 125 μm in diameter (for example, Shape Memory Alloy Wire, Flexinol125 LT, available from Mondo-tronics, Inc. of San Rafael, Calif.).Electrical connections to the ends of the shape memory alloy actuatorare made with 30 AWG copper wire. The copper wire is twisted to theshape memory alloy wire to effect a good electrical connection. Aplunger is machined out of acetal and has an overall length of 10.0 mmand a shaft diameter of 3.2 mm. An elastomer diaphragm is comprised of0.025 mm thick silicon rubber film (for example, Silicon Rubber Film,Cat. #86435K31, available from McMaster Carr, of Los Angeles, Calif.).The flat head of the plunger is secured to the elastomer diaphragm withepoxy (for example, Epoxy, Stock #14250, available from ITW Devcon, ofDanvers, Mass.). The ends of the shape memory alloy wire-copperconductor assembly are connected to the plunger and to the rigidrestraint with epoxy. A stainless steel biasing spring has an overalllength of 12.7 mm, an outside diameter of 3.0 mm, a wire diameter of0.35 mm and a spring constant of 0.9 N/mm (for example, Biasing Spring,Cat. # C0120-014-0500, available from Associated Spring, of Dallas,Tex.).

A pulse generating circuit is comprised of an adjustable analog timingcircuit based on a 556 dual timing integrated circuit (for example, 556Dual Timing Circuit, Part # TS3V556, available from ST Microelectronics,of San Jose, Calif.). Power is supplied by a 3 V lithium-manganesedioxide primary cell (for example, Li/MgO₂ Battery, Part # DL2032,available from Duracell, of Bethel, Conn.). Power load leveling isfacilitated by the use of an electrochemical supercapacitor (forexample, Electrochemical Supercapacitor, Part # B0810, available fromPowerStor Inc., of Dublin, Calif.) in parallel with the battery.High-power switching is achieved with a field effect transistor (forexample, Field Effect Transistor Switch, Part # IRLZ24N, available fromInternational Rectifier, of El Segundo, Calif.).

The functional model was characterized with respect to reproducibility,insulin stability and energy consumption. The model was operated byheating the shape memory alloy wire with a short pulse of current andthen allowing the shape memory alloy wire to cool. Each heating pulseand subsequent cooling period comprised a single actuation cycle.

A device that is used to automatically deliver a drug to an individualover an extended period of time should do so with extreme precision.This is particularly critical when the drug being delivered is one thatmight have dangerous health consequences associated with aninappropriate dose. Insulin is one such drug. An excessive dose ofinsulin can result in dangerously low blood glucose level, which in turncan lead to coma and death. Thus any device to be used for automaticallydelivering insulin to a diabetic person must be able to demonstrate avery high level of precision. To characterize the precision with whichthe invention can deliver insulin, the functional model was repeatedlycycled at a constant period of actuation and the total quantity ofliquid delivered was measured as a function of the number of actuationcycles. FIG. 5 shows typical results. The data in FIG. 5 were obtainedwith an actuation period of 28 seconds and a pulse duration of 0.15seconds. In FIG. 5 markers show actual data points and the linerepresents a least squares fit of the data points. Data were collectedover 8500 cycles at which point the measurement was stopped. The fit tothe data has a slope of 1.997 mg/cycle and a linear correlationcoefficient of 0.999 indicating that the functional model deliveredextremely consistent volumes of liquid with each actuation over thecourse of the measurement.

Another important requirement for any medical device that handlesinsulin is that the device does not damage the insulin. Insulin is alarge and delicate biomolecule that can readily be damaged by themechanical action (e.g., shear stress) of a pumping device. Three commonmodes of insulin destruction which result in a loss of bioactivity areaggregation, where individual insulin molecules bond together to formvarious polymer structures, degradation, where individual insulinmolecules are broken apart, and denaturing, where individual moleculesremain intact but lose their characteristic conformation. All threemodes of insulin destruction are exacerbated by elevated temperatures.Thus, in the development of a practical insulin pumping device,preferably, it should be demonstrated that the device does not damageinsulin. To characterize the insulin stability associated with theinvention, a quantity of insulin (Insulin, Humalog U100, available fromEli Lilly, of Indianapolis, Ind.) was set up to recycle continuouslythrough the functional model over the course of several days at 37° C.Samples of the insulin were collected each day for evaluation. Thisresulted in a series of pumped insulin samples with an increasing amountof pump stress. The insulin samples were then analyzed by reverse-phasehigh performance liquid chromatography. The chromatography indicated a2% loss of insulin concentration after a single pass through the pumpand a further loss of another 5% of the insulin concentration after 3days of recycling.

It is desirable for a small and inexpensive insulin delivery device tobe able to execute its maximum intended term of use with the energy froma single small inexpensive primary battery. Based on a 0.1 unit dosesize and a maximum insulin consumption of 100 units per day for 3 days,a maximum term of use for the inventive device might be considered to be3000 cycles. To characterize the energy consumption of the invention,the functional model was operated continuously for several days at anactuation period of 85 seconds while the voltage of a 200 milliamp-hour,2032 lithium/manganese dioxide battery was monitored. FIG. 6 showstypical results. A typical voltage vs. capacity curve for thelithium/manganese dioxide battery is characterized by an initial drop involtage from about 3.2 V to a plateau voltage of about 2.8 V. Thevoltage of the battery remains at this plateau level for the duration ofits useful life. The battery voltage will then drop precipitously to avalue below 2 V when its capacity expires. The data in FIG. 6 indicatethat the battery is still at its plateau voltage after 4000 pump cyclesand thus the 200 milliamp-hour, lithium/manganese dioxide battery ismore than adequate to power the device of the present invention for itsintended term of use.

ALTERNATIVE EMBODIMENTS OF THE INVENTION

A first alternative embodiment of the invention is diagrammedschematically in FIG. 7 and is comprised of all of the samesubcomponents and elements of the most general embodiment of theinvention shown in FIG. 1 with the following exceptions. In a firstalternative embodiment of the invention, the displacement cavity, aswell as the inlet and outlet conduit, are all comprised of a singlelength of small-diameter flexible and resilient tubing 701. The tubing701 is situated within a restraining fixture 702 secured to a rigid base703 so as to fix the position and orientation of the tubing 701 relativeto the other elements of the device. Inlet 704 and outlet 705 checkvalves are located within the bore of the tubing 701 such that they havea common orientation for flow direction and such that a length of emptytubing 701 exists in between the two check valves 704, 705. The volumewithin the inner diameter of the tubing 701 and in between the two checkvalves 704, 705 comprises a displacement cavity 706. The volume of thedisplacement cavity 706 is varied by compressing the resilient tubing701 with a plunger 707 (described below) at a position midway betweenthe two check valves 704, 705. The volume within the inner diameter ofthe tubing 701 and in between the two check valves 704, 705 when thetubing 701 is uncompressed defines the maximum volume of displacementcavity 706. The volume within the inner diameter of the tubing 701 andin between the two check valves 703, 704 when the tubing 701 is fullycompressed by the plunger 707 defines the minimum volume of thedisplacement cavity 705.

The plunger 707 is comprised of a cylindrical length of rigid dielectricmaterial and includes a flange 708 and a tapered end 709. The plunger707 is situated within a cylindrical bore 710 of a rigid restraint 711such that the axis of the plunger 707 is oriented normal to the axis ofthe resilient tubing 701 and such that the tapered head 709 of theplunger 707 may be alternately pressed against the resilient tubing 701and removed from contact with the resilient tubing 701 with movement ofthe plunger 707 along a line of motion coincident with the its axis. Abiasing spring 712 is fitted around the shaft of the plunger 707 inbetween the rigid restraint 711 and the plunger flange 708. The relativepositions and dimensions of the plunger 707, the rigid restraint 711 andthe biasing spring 712 are such that at equilibrium the biasing spring712 exerts a force on the plunger 707 along a line coincident with itsaxis that is sufficient to fully collapse the resilient tubing 701 andthus create a state of minimum volume of the displacement cavity 706.

A straight length of shape memory alloy wire 713 is situated in aposition coincident with the axis of the plunger 707. One end of theshape memory alloy wire 713 is attached to the rigid base 703 andelectrically connected by connection 716 to the pulse generating circuit714 and the electric power source 715. The other end of the shape memoryalloy wire 713 along with an electrical connection 717 to that end isattached to the shaft of the plunger 707. The shape memory alloy wire713 is of sufficient length and strength that when heated so as toinduce phase transition and associated dimensional change it will pullthe plunger 707 away from contact with the resilient tubing 701 againstthe opposing force of the biasing spring 713.

A second alternative embodiment of the invention is diagrammedschematically in FIG. 8 and is comprised of all of the samesubcomponents and elements of the most general embodiment of theinvention shown in FIG. 1 with the following exceptions. A displacementcavity 801 is comprised of a cylindrical shell 802 and tube 803arrangement where the tube 803 is coaxial with the shell 802 and canmove freely within the shell 802 along a line coincident with that axis.The volume of the displacement cavity 801 is varied by moving the tube803 relative to the shell 802. Movement of the tube 803 into the shell802 reduces the volume of the displacement cavity 801 whereas movementof the tube out of the shell increases the volume of the displacementcavity 801. A dynamic seal 804, for example and elastomer o-ring, sealsthe displacement cavity 801 while not interfering adversely with therelative motion of the shell 802 and tube 803. Outlet 805 and inlet 806conduits access the displacement cavity 801 through the ends of theshell 802 and tube 803 respectively. Outlet 807 and inlet 808 checkvalves are situated within the shell 802 and tube 803 respectively. Abiasing spring 809 is situated within the displacement cavity 801 so asto resist the motion of the displacement cavity 801 toward a state ofreduced volume. A shape memory alloy wire 810 is attached between theshell 802 and the tube 803 along the outside of the assembly such thatwhen the shape memory alloy wire 810 is heated so as to induce phasetransition and associated dimensional change it will incline thedisplacement cavity 801 toward a state of reduced volume. The shapememory alloy wire 810 is electrically connected by connector 811 to aprogrammable pulse generating circuit 812 and a source of electric power813. Hard stops (not shown) on the limits of the relative positions ofthe shell 802 and tube 803 define the maximum and minimum volumes of thedisplacement volume 801.

Operation of both the first and second alternative embodiments of theinvention proceed in a manner analogous to that described for the mostgeneral embodiment and preferred embodiment of the invention.

In all of the embodiments described above, a shape memory alloy wireacts as an actuator to drive a movable member to increase or decreasethe fluid volume in the pump head, and once the wire cools a spring isused to return the movable member back to its original position. Thoseof reasonable skill in this field will appreciate that a multitude ofother biasing means exist, one or more of which can be used in place ofor in addition to the spring. In fact, a shape memory alloy can beconstructed in such a way that it drives the movable member in bothdirections to act as both an actuator and a return biasing element. Forexample, the shape memory alloy can be coiled much like a spring todrive the movable member in one direction when heated and in the otherdirection when cooled.

A first alternative embodiment of a pulse generating circuit isdiagrammed schematically in FIG. 9 and is comprised of a 200milliamp-hour lithium-manganese dioxide primary battery 901, a DC to DCconverter 902, a capacitor 903, a low-resistance field effect transistorswitch 904, a programmable digital timing circuit 905, an inductor 906and a diode 908. The shape memory alloy wire is indicated in FIG. 9symbolically as a resistor 907. The objective of this embodiment of apulse generating circuit is that the pulses of power delivered to theshape memory alloy wire 907 can be of a higher voltage, and thus highercurrent, than that associated with the preferred embodiment of a pulsegenerating circuit diagrammed in FIG. 4 and described previously. A highvoltage, high current power pulse has the advantage that it can actuatethe circuit in a shorter more efficient time period. Additionally, thealternative embodiment of a pulse generating circuit allows the usefullife of the battery 901 to be extended to a lower voltage and canprevent other circuitry powered by the battery from resetting when thebattery voltage droops as is likely to happen in the preferredembodiment. The battery 901 and capacitor 903 are electrically connectedto each other in parallel through the DC to DC converter 902. Thecapacitor 903 is further connected to the shape memory alloy wire 907through the transistor switch 904. The programmable timing circuit 905,also powered by the battery 901 sends a gating signal to the transistorswitch 904 as programmed by the user in accordance with their pumpingrequirements. During the period for which the transistor switch 904 isopen, the DC to DC converter 902 draws energy from the battery 901 andstores it in the capacitor 903. Use of the DC to DC converter 902 allowsthe voltage of the capacitor 903 to be charged to a significantly highervalue than that associated with the battery 901 and to be charged to thesame voltage throughout the life of the battery 901 regardless of thebattery voltage. It is intended that the transistor switch 904 may bemodulated to send an overall energy pulse as a single pulse or as asequence of discrete smaller pulses. It is intended that these smallerpulses may be sequenced so as to tailor a custom profile for the overallenergy pulse. The custom profile would ensure optimal energy delivery tothe shape memory alloy without exceeding its fusing characteristics. Theinclusion of the inductor 906 and diode 908 allows current to continueto flow through the shape memory alloy wire 907 after the transistorswitch 904 is opened when the pulse is modulated. This allows furthercontrol of the energy delivered to the shape memory alloy.

Various references, publications, provisional and non-provisional UnitedStates patent applications, and/or United States patents, have beenidentified herein, each of which is incorporated herein in its entiretyby this reference. Various aspects and features of the present inventionhave been explained or described in relation to beliefs or theories orunderlying assumptions, although it will be understood that theinvention is not bound to any particular belief or theory or underlyingassumption. Various modifications, processes, as well as numerousstructures to which the present invention may be applicable will bereadily apparent to those of skill in the art to which the presentinvention is directed, upon review of the specification. Although thevarious aspects and features of the present invention have beendescribed with respect to various embodiments and specific examplesherein, it will be understood that the invention is entitled toprotection within the full scope of the appended claims.

1. A device for pumping a predetermined volume of fluid, comprising: acavity operably associated with an inlet and an outlet, the inlet of aconstruction sufficient for operable communication with a source offluid; an inlet check valve operably associated with the inlet and anoutlet check valve operably associated with the outlet; a plungeroperably associated with the cavity, the plunger disposed in a firstposition by way of a biasing force and moveable therefrom to a secondposition, the plunger sufficient to compress the resilient enclosurewhen in one of the first position and the second position, andsufficient to decompress the resilient enclosure when in a different oneof the first position and the second position; a biasing elementoperably associated with the plunger and of a construction sufficient toprovide the biasing force; an actuator including a shape memory alloy,the actuator operably associated with the plunger to move the plungerfrom the first position to the second position when the shape memoryalloy partially undergoes a thermally induced transformation relative toan original condition thereof, and to move the plunger from the secondposition to the first position when the shape memory alloy returnstoward the original condition; and wherein the plunger draws fluid intothe cavity when the plunger moves from the first position to the secondposition.
 2. The device of claim 1, wherein a phase transformationtemperature of the shape memory alloy is about 70° C. above ambienttemperature.
 3. A device for pumping a predetermined volume of fluid,comprising: a cavity operably associated with an inlet and an outlet,the inlet of a construction sufficient for operable communication with asource of fluid; an inlet check valve operably associated with the inletand an outlet check valve operably associated with the outlet; a plungeroperably associated with cavity, the plunger urged to a first positionby a biasing force and moveable therefrom to a second position, whereinthe plunger travels to compress the cavity when in the first position tofully decompress the cavity when in the second position; a biasingelement operably associated with the plunger to provide the biasingforce; an actuator including a NiTi alloy having a high first transitiontemperature and a low second transition temperature, wherein theactuator operably associated with the plunger moves the plunger from thefirst position to the second position when the NiTi alloy thermallytransforms at the high first transition temperature, and moves theplunger from the second position to the first position when the NiTialloy thermally transforms at the low second transition temperature andreturns toward the original condition; and wherein the plunger drawsfluid into the cavity when the plunger moves from the first position tothe second position.
 4. The device of claim 3, wherein the high firsttransition temperature is about 70° C. above ambient temperature.
 5. Thedevice of claim 3, wherein the actuator includes a NiTi alloy wire thatis partially heated on an end for a phase transformation in a portion ofthe wire proximate that end.
 6. A method of pumping a predeterminedvolume of fluid, comprising: providing a cavity operably associated withan inlet and an outlet; providing an inlet check valve operablyassociated with inlet, and an outlet check valve operably associatedwith the outlet; providing a plunger in a first position under bias viaa biasing element; providing a shape memory alloy having first andsecond transition temperatures, operably associated with the plunger;providing at least one pulse of electricity to thermally transform theshape memory alloy at the first transition temperature to move theplunger to a second position; and ceasing the providing of at least onepulse of electricity to the shape memory alloy for cooling to the secondtransition temperature to return the plunger to the first position underbias of the biasing element; the cavity being compressed when theplunger is in one of the first position and the second position, andbeing decompressed when the plunger is in a different one of the firstposition and the second position; and wherein the plunger draws fluidinto the cavity when the plunger moves from the first position to thesecond position.
 7. The method of pumping a predetermined volume offluid according to claim 6, wherein multiple pulses of electricity areapplied to the shape memory alloy to thermally transform the shapememory alloy at least at the first transition temperature.
 8. The methodof pumping a predetermined volume of fluid according to claim 6, whereinthe first transition temperature is about 70° C. above ambienttemperature.
 9. The method of pumping a predetermined volume of fluidaccording to claim 6, wherein the fluid includes insulin.
 10. The methodof pumping a predetermined volume of fluid according to claim 6, whereinthe method further comprises joining a fluid reservoir in communicationwith the cavity, wherein the fluid reservoir is contained in acollapsible, resilient enclosure.
 11. A device for pumping apredetermined volume of fluid, comprising: a fluid reservoir containedwithin an enclosure, wherein the enclosure is collapsible; adisplacement cavity in communication with the fluid reservoir; a fluidinlet and a fluid outlet in communication with the displacement cavity;a plunger acting on the cavity; a shape memory actuator, having a firsttransition temperature to a high temperature phase with a rememberedconfiguration and a second transition temperature to a low temperaturephase with a malleable configuration, linked to the plunger; a biasingelement linked to the plunger; and an electrical source providing acurrent to the shape memory actuator, wherein a current on statetransforms the shape memory actuator to the high temperature phase andmoves the plunger to a first position within the cavity, and a currentoff state allows the shape memory actuator to cool to the lowtemperature phase so that a biasing element moves the plunger to thesecond position within the cavity.
 12. A device for pumping apredetermined volume of fluid according to claim 11, wherein the shapememory actuator in the remembered configuration has a greater lengththan in the malleable configuration.
 13. A device for pumping apredetermined volume of fluid according to claim 11, wherein the shapememory actuator in the remembered configuration compresses the cavity inthe first position and the biasing element decompresses the cavity inthe second position.
 14. A device for pumping a predetermined volume offluid according to claim 11, wherein the shape memory actuator in thehigh temperature phase has a shorter length than in the low temperaturephase.
 15. A device for pumping a predetermined volume of fluidaccording to claim 11, wherein the shape memory actuator in the hightemperature phase has a longer length than in the low temperature phase.16. A device for pumping a predetermined volume of fluid according toclaim 11, wherein the shape memory actuator includes nitinol, and in thehigh temperature phase, has substantially transformed into theaustentitic phase.
 17. A device for pumping a predetermined volume offluid according to claim 11, wherein the shape memory actuator includesnitinol, and in the low temperature phase, has substantially transformedinto the martensitic phase.
 18. A device for pumping a predeterminedvolume of fluid, comprising: a fluid reservoir contained within anenclosure; a displacement cavity in communication with the fluidreservoir; a fluid inlet and a fluid outlet in communication with thedisplacement cavity; a plunger acting on the cavity; a shape memoryactuator, having a first transition temperature to a high temperaturephase with a remembered configuration and a second transitiontemperature to a low temperature phase with a malleable configuration,linked to the plunger; a biasing element linked to the plunger; and anelectrical source providing a current to the shape memory actuator,wherein a current on state transforms the shape memory actuator to thehigh temperature phase and moves the plunger to a first position withinthe cavity, and a current off state allows the shape memory actuator tocool to the low temperature phase so that a biasing element moves theplunger to the second position within the cavity; and wherein at leastthe enclosure and displacement cavity are disposable and housed discretefrom the plunger, actuator, biasing element, and electrical source. 19.A device for pumping a predetermined volume of fluid according to claim18, wherein the shape memory actuator includes a wire having a diameterof about 125 μm.
 20. A device for pumping a predetermined volume offluid according to claim 18, wherein the shape memory actuator includesa wire having a length of about 40 mm.